The present invention relates to a series of new oxazolidine derivatives, which exhibit valuable anti-diabetic and anti-obesity activities, rendering the compounds suitable for use in the treatment or prevention of hyperlipemia and hyperglycemia, and, by inhibiting the action of aldose reductase, they can also be effective in the treatment and prevention of complications of diabetes. They are also effective in the treatment and prophylaxis of obesity-related hypertension and osteoporosis. The invention also provides processes for preparing the compounds of the present invention, as well as methods and compositions using them.
Thiazolidine derivatives, which are structurally related to the compounds of the present invention and are active in reducing blood sugar levels are known and are described in, for example, Japanese Patent Application Kokai No. Sho 55-22636 (Tokko No. Sho 62-42903); Japanese Patent Application Kokai No. Sho 60-51189 (Tokko No. Hei 2-31079); Kawamatsu et al., Chem. Pharm. Bull., 30, (1982) 3580-3600 and European Patent Publication No. 441,605.
European Patent Publication No. 294,995 and PCT WO 92/07838, which are currently thought to represent the closest prior art, disclose compounds which are structurally similar to those of the present invention. The compounds from these two prior art documents which are believed to be structurally the closest to the compounds of the present invention are represented by formula (M) and formula (N), below. The compound of formula (M), which is 3-{2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenyl]-1-methylethyl}-5-(3-chlor ophenyl)oxazolidin-2-one, is described in European Patent Publication No. 294,995, and the compound of formula (N), which is 3-{2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxy]ethyl}-5-phenyloxazolidin -2-one, is described in PCT WO 92/07838. ##STR2##
The compounds of the prior art do, however, have limited activity. There is therefore still a need for compounds with improved activity and toxicity characteristics.
We have now discovered a limited series of novel oxazolidine derivatives which have valuable anti-diabetic and anti-obesity activities, as well as being suitable for treating conditions associated with obesity and diabetes, and which have a low toxicity.